Full Dose Paclitaxel Plus Vinorelbine as Salvage Chemotherapy in Anthracycline-Resistant Advanced Breast Cancer: A Phase II Study

Polyzos, A.; Tsavaris, Nicolas; Kosmas, Christos; Gogas, Helen; Toufexi, Helen; Kosmidis, Chris; Markopoulos, Christos; Γιαννόπουλος, Αθανάσιος; Papadopoulos, Othon; Stamatiadis, D.; Kouraklis, Gregory

doi:10.1179/joc.2003.15.6.607

Cited by 19 publications

(3 citation statements)

References 21 publications

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“…The schedule variable also interacted with the ratio of docetaxel and vinorelbine, suggesting that the ratio was only important if the clinicians chose to intersperse single drug doses between treatments with the combination of drugs (test 8, Table IV). The results of the tests were similar when additional trials, mainly with paclitaxel substituted for docetaxel, were included in the dataset (57,(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77).…”

Section: Analysis Of Chemotherapy Clinical Trialssupporting

confidence: 52%

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Uppal

Li²,

Wendt³

et al. 2007

Int J Oncol

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Abstract. Subcellular distribution of mass can be analyzed by a technique that involves culturing cells on interferometers and digitizing their interference contours. Contour sampling resulted in 102 variables per cell, which were predictors of oncogenic transformation. Cell phenotypes can be deconstructed by use of latent factors, which represent the covariance of the real variables. The reversal of the cancertype phenotype by a combination of microtubule-stabilizing and -depolymerizing agents was described previously. The implications of these results have been explored by clinicians who treated patients with the combination of docetaxel and vinorelbine (Navelbine ® ). The current study was performed to determine the effects of different combinations on phenotype and in phases of the cell cycle other than mitosis. Combinations of paclitaxel with either colchicine, podophyllotoxin, nocodazole, or vinblastine caused phenotype reversal. Paclitaxel analogue, 7-deoxytaxol, by itself caused reversal. Factors #4, (filopodia), #5 (displacement and/or deep invaginations in the periphery), #8, and #12 took on values typical of normal cells, whereas the values of #7 (p21-activated kinase), and #13 (rounding up) shifted toward the cancer-type. All combinations altered microtubule arrangement at the cell edge. Delivery schedules and drug ratios used in clinical studies were subjected to analysis. Clinical response rates were better when the combination was not interspersed with a single agent (P=0.004). The results support the idea that efficacy depends upon simultaneous exposure to both agents, and suggest a novel mechanism for combination therapies. These therapies appear to restore in transformed cells some of the features of a contactinhibited cell, and to impede progress through the cell cycle even when provided at nanomolar concentrations.

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Section: Analysis Of Chemotherapy Clinical Trialssupporting

confidence: 52%

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Uppal

Li²,

Wendt³

et al. 2007

Int J Oncol

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“…Polyzos and colleagues conducted a Phase II study of salvage therapy in anthracycline-resistant breast cancer patients using paclitaxel and vinorelbine (Tables 1 and 2). 29 They observed a 33% response rate and 8-month median survival and commented that this indicates a lack of cross-resistance between this chemotherapy combination and anthracyclines. Despite use of SC amifostine and G-CSF, 35% of patients developed grade 3 to 4 neutropenia, although no grade 3 to 4 neuropathy was observed.…”

Section: Recent Research: Amifostine and Chemotherapy Regimensmentioning

confidence: 99%

Commentary: The Pharmacological Antioxidant Amifostine—Implications of Recent Research for Integrative Cancer Care

Block

Gyllenhaal

2005

Integr Cancer Ther

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Amifostine is a pharmacological antioxidant used as a cytoprotectant in cancer chemotherapy and radiotherapy. It is thought to protect normal tissues relative to tumor tissue against oxidative damage inflicted by cancer therapies by becoming concentrated at higher levels in normal tissues. The degree to which amifostine nevertheless accumulates in tumors and protects them against cancer therapies has been debated. Guidelines have been published that direct its use in chemotherapy and radiation, taking into consideration the concerns of tumor protection. In this article, clinical studies of amifostine appearing since the publication of the most recent set of guidelines are reviewed. Randomized and nonrandomized trials of regimens involving chemo-therapeutic agents (chemotherapy, chemoradiation, conditioning regimens for bone marrow transplant) are discussed. Nineteen studies showed positive effects for amifostine reducing the level of side effects of these regimens, while 9 showed no effect and 1 had a questionable result. Clinically relevant levels of amifostine toxicity were observed in several studies, but subcutaneous administration may reduce such toxicity. Amifostine showed protection against mucositis, esophagitis, neuropathy, and other side effects, although protection against cisplatin-induced ototoxicity was not observed. No evidence of tumor protection was observed. Amifostine may enable populations unable to tolerate conventional cancer therapy to receive treatment of their cancers, even if some degree of tumor protection is eventually discovered. The authors discuss the implications of this research for patient populations seen in integrative cancer care centers and for research on phytochemical antioxidants such as vitamins and carotenoids.

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“…A large number of phase II trials have been performed which have generally shown encouraging activity with an acceptable safety profile (Table 3). Examples include Paclitaxel 30–37 Docetaxel; 38–46 Doxorubicin; 47–51 Epirubicin 52–54 Mitoxantrone; 55–57 Pegylated Liposomal Doxorubicin; 14,58–61 Gemcitabine; 62–73 5-Fluorouracil; 74–79 platinum compounds; 80–83 and Capecitabine, 84–88 which will be separately discussed. Several triplets have also been investigated but increased toxicity should be expected.…”

Section: Introductionmentioning

confidence: 99%

A Review of Vinorelbine in the Treatment of Advanced Breast Cancer

Brunello

Roma

Basso

et al. 2009

Clinical Medicine. Therapeutics

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Abstract:Vinorelbine is a semi-synthetic vinca alkaloid that has been shown active in many tumor types and is currently registered for the treatment of advanced breast cancer (ABC) and non-small cell lung cancer (NSCLC), and it is used in other cancer type such as prostate cancer, lymphomas, gynecologic malignancies. This agent has a generally favorable safety profile, and may be suitable for use in special populations such as the elderly and/or frail patient. However, with the taxanes established as standard second line treatment for ABC after failure of an anthracycline, Vinorelbine has been generally relegated for use as third line therapy, in competition with the oral compound Capecitabine. Combination regimens of Vinorelbine and Gemcitabine have been indeed widely studied, and have been demonstrated to be safe and effective. More recently, the exciting results observed with the combination of Vinorelbine and Trastuzumab in patients with Her-2 overexpressing tumors, as well as the development of a reliable formulation and revised schedule of oral Vinorelbine appear to have revived the interest in this compound in the management of this disease. Yet, data from properly designed randomized clinical trials are eagerly awaited to confirm the amount of available data which are mostly based on phase II studies.

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Full Dose Paclitaxel Plus Vinorelbine as Salvage Chemotherapy in Anthracycline-Resistant Advanced Breast Cancer: A Phase II Study

Cited by 19 publications

References 21 publications

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Commentary: The Pharmacological Antioxidant Amifostine—Implications of Recent Research for Integrative Cancer Care

A Review of Vinorelbine in the Treatment of Advanced Breast Cancer

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